[A case of hypercalcemia in hemodialysis]. / Un caso di ipercalcemia in emodialisi.

We report a case of hypercalcemia in a female patient who was restarted on hemodialysis 22 years after renal transplantation. Graft biopsy showed chronic post-transplant nephropathy. Treatment with immunosuppressants and steroids was maintained owing to residual graft function. She was then given oral paracalcitol 1 µg/d for secondary hyperparathyroidism (iPTH 850 pg/mL) and her transplant medication was reduced and then discontinued. After this, the patient referred widespread joint pain, especially in the hips and subsequently presented with erythema nodosum. She also developed hypercalcemia and hyperphosphatemia which persisted after stopping paracalcitol. The clinical picture of increased serum calcitriol, with depressed PTH, suggested sarcoidosis, despite normal ACE levels, a chest X-ray and skin biopsy confirmed the diagnosis, and the patient was started on prednisone 50 mg/day, resulting in prompt normalization of both symptoms and blood chemistry. This is a rare case of hypercalcemia secondary to sarcoidosis in an uremic patient. The sarcoidosis was most likely suppressed by the transplant therapy and rapidly developed after this was suspended. Prompt diagnosis resulted in a good therapeutic response.

Endoscopic ultrasound-fine needle aspiration (EUS-FNA) for pancreatic lesions: effectiveness in clinical practice.

BACKGROUND: Diagnosis of pancreatic masses is often difficult. Endoscopic ultrasound-fine needle aspiration has been proposed as the best single-step strategy. AIMS: To prospectively evaluate feasibility, effectiveness and safety of endoscopic ultrasound-fine needle aspiration of pancreatic masses in a consecutive study of unselected patients. METHODS: Two hundred ninety-three patients were enrolled in two referral Hospitals in Northern Italy. All patients were referred either due to the presence of imaging test abnormalities (suspected or evident masses, or features indirectly suggesting the presence of a mass) or due to clinical or biochemical findings suggesting pancreatic cancer in the absence of positive imaging. All patients underwent linear array endoscopic ultrasound and, when indicated, fine needle aspiration. All procedures were recorded prospectively. The final diagnosis was established at the end of follow-up or when the patients underwent surgery or died. RESULTS: Fine needle aspiration was indicated in 246 of 293 cases (84%), considered technically feasible in 232 of 246 cases (94%) and gave adequate samples for histopathological diagnosis in 204 of 232 cases (88%). Endoscopic ultrasound sensitivity, specificity and accuracy were 79, 60 and 72%, respectively; the corresponding figures for endoscopic ultrasound-fine needle aspiration were 80, 86 and 82%. There was good agreement with final diagnosis for endoscopic ultrasound-fine needle aspiration (kappa 0.673, 95%CI 0.592-0.753), greater than that for endoscopic ultrasound alone (kappa 0.515, 95%CI 0.425-0.605). There was one case of intracystic haemorrhage and one case of transient hyperthermia (0.3%). CONCLUSIONS: Endoscopic ultrasound-fine needle aspiration of pancreatic masses seems to be feasible, effective and safe in this consecutive study of patients.

The hazardous burden of Herpesviridae in inflammatory bowel disease: the case of refractory severe ulcerative colitis.

BACKGROUND: Herpesviridae infection or spread may be a hazard in immunodepressed patients. In the field of inflammatory bowel disease, refractory severe ulcerative colitis is a challenging condition, closely associated to immunosuppression both for inanition due to the disease activity and for immunosuppressive treatments. Cytomegalovirus (CMV) has been proposed as a major cause of refractoriness, while other Herpesviridae may be a risk factor in the long-term follow-up. AIM OF THE STUDY: To evaluate the positivity rates of CMV, Epstein-Barr (EBV) and Human herpes virus-8 (HHV8) in a consecutive group of ulcerative colitis patients who underwent colectomy for refractoriness to medical treatment compared to a control group, using state of the art methods. PATIENTS AND METHODS: Colonic specimens from 24 consecutive patients with ulcerative colitis submitted to colectomy for refractoriness and from 20 controls (submitted to colectomy for colorectal cancer) were studied. Standard histology and immunohistochemistry (IHC) for CMV and specific polymerase chain-reaction (PCR) for CMV, EBV and HHV8 were carried out. RESULTS: Regarding CMV, 1 case (4%) was positive at histology and IHC, whereas 3 cases (13%) were positive at PCR, compared to none in the control group (p=0.239). For EBV 2 cases (8%) and 2 controls (10%) were positive at PCR. None of the cases or of controls was positive for HHV8. The only clinical characteristic independently associated to CMV positivity was the white blood cell count at admission, higher among CMV positive patients (p<0.001). At the end of the post-surgery follow-up (median 7.3 years) none of the CMV positive cases experienced pouchitis, compared to 3/21 (14%) of the CMV negative cases (p=1.000). DISCUSSION: Our data suggest that CMV is uncommon (13%), even though PCR techniques, considered to be the most sensitive tools, were used for virus detection and the study population is made by highly selected patients with definite refractoriness. EBV and HHV8 may represent a theoretical risk of immunosuppressive therapy because of their potential role as cancer triggers; however in our study, results seem to be reassuring that UC patients undergoing immunosuppressive therapy are not exposed to an excessive risk of viral infection.

[Mechanical characteristics of the human bladder wall and application of the results in a finite elements model to study the pelvic floor]. / Studio delle caratteristiche meccaniche della vescica umana e applicazione in un modello agli elementi finiti per lo studio del pavimento pelvico.

AIM: There is no radiological method capable of providing a real-time, dynamic 3D illustration of the pelvic organs and supporting structures during stress, physiological regressions and pathological alterations. This paper describes the determination of the mechanical characteristics of the human bladder, the application of the results in a numerical 3D finite elements model of the pelvis and the processing of the model in the presence or absence of urethro-pelvic and pubo-vescical ligaments supporting the pelvis. METHODS: A 3D numerical finite element model of the human pelvis has been realised starting from CT image and Mimics (Materialise), Rhinoceros (Robert Mc Neel and Associates), Patran (MSC) e Marc (MSC) programs. The mechanical characteristic of human bladder specimen have been studied in vitro drawn up from human bladder removed for neoplasia. Results have been introduced in a numeric model. After the definition of bond and load applied, we made the simulation and numerical structural analysis with and without some ligaments that link pelvic fascia and urethra at the pubis. RESULTS: The study of mechanical data of bladder reports structural differences between lateral wall, trigone wall and anterior wall in correlation to the topographical disposition of fibres of detrusor and its thickness. Dynamics investigation performed in the absence of cervical urethra ligaments of suspension and pelvic fascia showed that the anatomical deflections of pelvic fascia modified the distributions of loads toward centripetal deviation, stressing even more the perineal area and the sphincter tract. CONCLUSIONS: The study shows that trigone is the area with the greatest stiffness in comparison with other areas of the bladder and that it has the greatest strength to tensile loads. This study has shown that pelvic fascia, urethropelvic and pubovescical ligaments are cardinal supports that cannot be neglected in a dynamic numerical analysis. Dynamic simulation of the model in the absence of the ligaments confirms the role of surgical techniques used for their reconstruction following their section during radical surgery.

Multiple sampling 13C-urea breath test: improvement of diagnosis in postgastrectomy patients.

AIM: Partial gastrectomy and Helicobacter pylori (H. pylori) infection are considered 2 risk factors for gastric cancer development. False negative urea breath test (UBT) results have been described in patients with gastric surgery, due to rapid gastric emptying of urea solution from the stomach. On the other hand, a rapid 10-minute 14C-UBT proved to be highly reliable for diagnosis of H. pylori infection when delaying test meal was omitted. Aim of this study was to improve the diagnostic accuracy of 13C-UBT in patients with gastric resection. METHODS: UBT was performed in 100 gastrectomised patients with breath collection at 0, 10, 15, 20, 25 and 30 minutes (multi-UBT) after 100 mg 13C urea ingestion and 100 ml of marketed fruit juice. In 28 cases contemporary histological data from biopsy specimens (within 1 month, in absence of treatment) were also available. RESULTS: Multi-UBT was persistently negative or positive in all the samplings in 34% and 25% of cases, respectively. Positivity only at 30 minutes was found in 10% of cases, while 19% of subjects were positive at 15-25 minutes but not at 30 minutes. In 12% of cases the test was positive only at 10 minutes. CONCLUSIONS: Multi-UBT offers a not negligible diagnostic improvement over the standard UBT: at least 19%, and up to 31% if positivity at ''10-minute only'' is taken into account. This method can be useful when accurate diagnosis of H. pylori infection is required in gastrectomised patients.

Thyroid cancer histotype changes as observed in a major general hospital in a 21-year period.

The existing registries of thyroid carcinoma are seldom comparable as far as epidemiological data, diagnostic criteria and histopatological description are concerned. Epidemiological studies report a progressive increase in the incidence of thyroid carcinoma in the last twenty years and in both sexes this increase of incidence has been referred to papillary histotype. Data collected from surgical series show a rate of thyroid carcinomas from 7 to 20% of total thyroid surgeries. The present study was designed in order to obtain a retrospective review of the distribution of thyroid carcinoma's different histotypes in the last 21 years in a major General Hospital. Detailed analysis of patients with histologically confirmed thyroid carcinoma admitted between 1974 and 1994 to the Surgery Department of Mauriziano Hospital of Torino, Italy showed an overall 11.8% prevalence of thyroid cancer out of the total thyroid surgeries. The rate of papillary carcinoma was the highest (54.3%) followed by follicular carcinoma (27.6%), anaplastic carcinoma (11.1%), medullary carcinoma (4.6%) and others (2.4%). The papillary-to-follicular ratio varied from 0.60 in 1974-76 to 6.88 in 1992-94. Female to male ratio of all thyroid carcinoma histotypes was 2.0 or more; papillary and follicular histotypes had the highest ratio. The variations of the histotype rate observed may be consequence of the silent increase of daily iodine intake throughout the subsequent years, while improved diagnostic tools available and increased experience of the medical staff have probably increased the number on thyroid ablations performed. Our data confirm the changing epidemiology of thyroid carcinoma, reported by international literature.

[Pancreatic beta-cell hyperplasia in adults. A clinical case]. / L'iperplasia delle beta-cellule pancreatiche nell'adulto. Caso clinico.

The author describe a rare case of pancreatic beta-cell hyperplasia. The patient was referred to us because of serious hypoglycemic crises. During hospitalization, endogenous hyperinsulinism was confirmed by hematochemical and instrumental tests. AngioCT of the pancreas evidenced a small lesion of the corpus, suspected of insulinoma. The patient underwent a corpus caudalis pancreatectomy: a small nodule with histologic neuroendocrine traits was ablated. A few days after the operation, new symptomatic hypoglycemia appeared. The hormonal tests confirmed a recurrence of endogenous hyperinsulinism. The patient underwent a new operation for pancreaticoduodenectomy: histological examination confirmed a pancreatic beta-cells hyperplasia. This condition has to be taken into account in the differential diagnosis of post prandial hypoglycemia. Besides, the observation of an insulinoma doesn't exclude the presence of a diffused disorder of islet cells as in the case above described.

[Wegener's granulomatosis. Diagnosis and follow-up of 7 cases]. / Granulomatosi di Wegener. Diagnosi e follow-up di 7 casi.

Wegener's granulomatosis (WG) is a rare small vessels necrotizing and granulomatous systemic vasculitis which usually affects the respiratory-tract and the kidneys. Diagnosis is often difficult, but has become easier with antineutrophil cytoplasmic antibodies (ANCA) detection that may justify a more aggressive biopsy policy also in the elderly. Classic treatment with steroids and oral cyclophosphamide (CY) has proven to be of benefit, but side-effects are severe and frequent and the search for less toxic therapeutic schemes should be encouraged. We treated with intravenous pulses of CY (1 g/m2 monthly for 6 months, every two months for the following 6 and quarterly for another year) 5 of 7 patients with WG recently admitted to our institution. We obtained a quick, complete response in 4 of these patients, with no side effects, nor relapses, after a mean follow-up of 17 months. The only patient who did not respond was identified soon after the beginning of the treatment because of a poor reduction of ESR and could be shifted to oral administration of CY successfully. From our still limited experience CY intravenous pulses have proven to be safe and effective enough to advice its use as the first-choice treatment for WG.

[Renal damage in rheumatoid arthritis]. / Il danno renale in corso di artrite reumatoide.

Renal damage is not uncommon in rheumatoid arthritis, but the causative role of the disease per se is not well defined yet. In this paper the updated literature data are reported and our own experience as well. In particular, we describe renal syndromes associated with non-steroidal antiinflammatory drugs, remission-inducing agents (gold and penicillamine) and cytotoxic drugs, secondary amyloidosis, systemic rheumatoid vasculitis, glomerular and tubulo-interstitial nephritis not related to drug therapy.

[Prognostic factors in adenocarcinoma of the endometrium]. / Fattori prognostici nell'adenocarcinoma dell'endometrio.

We report the results of the combined use of surgery and radiation therapy in the treatment of endometrial carcinoma. From January 1974 to December 1989, 89 cases were treated by means of abdominal hysterectomy followed by external radiation therapy. Actuarial survival at 5 years is 100% for stage I, 75% for stage II, and 42.86% for stage III; stage IV patients could not be evaluated. Prognostic factors were statistically significant. In stages II and III survival rates were directly related to histological grading (G1: 90.91%; G2: 81.82%; G3: 25%) and to myometrial infiltration (M1: 85.71%; M2: 81.82%; M3: 70%). Generally, survival was related to age, and prognosis was better in younger patients (under 55) and depended on lymph nodal involvement (N-: 88.24%, versus N+: 25%). Vaginal and pelvic recurrences were 8 (10.1%), and deaths were 13. The identification of high-risk patients will make it possible to select an even more adequate treatment.

Immunological features of endemic goiter.

Some immune aspects of simple endemic goiter have been studied through a comparison of IgG, IgA, IgM, kappa and lambda chains, and C3 and C4 in the peripheral blood of 59 patients operated on for goiter and the peripheral blood of 49 normal controls. The median IgM was lower in the goiter blood. The incidence of thyroglobulin (Tg) and microsomal (Mi) antibodies (Abs) was 20.3% in goiter blood and that of nonthyroid autoAbs was 37%. Active and total rosetted blood lymphocytes were counted and OKT3, OKT4, OKT8, Leu 1, Leu3a, Leu2b, T DR+, and NK cell populations were classified. Helper T cells were occasionally decreased when goiter was associated with lymphocytic thyroiditis. The NK percentage was sometimes higher in goiter blood, whereas the T DR+ percentage was not significantly different in the two groups. Lymphocyte infiltration (LI) was noted in 32% of goiters (about 5% with a diffuse and nodular pattern). A prevalence of helper/inducer cells was observed among the infiltrating T cells. HLA-DR antigen (Ag) positive epithelial cells were seen, not only in LI areas. Granular deposits of IgG, IgA, IgM, and C3 on the follicular basal membrane were stained in 6.7% of goiters Patterns histologically and immunologically similar to those in Hashimoto's thyroiditis may therefore be observed in long-standing simple endemic goiter, suggesting that an autoimmune mechanism may be involved in its pathogenesis.

Serum autoantibodies and thyroid lymphocytic infiltration in endemic goitre.

Patients with thyroid diseases from areas of endemic goitre in Northern Italy were examined for thyroid antibodies by passive haemoagglutination. Of 40 schoolboys with goitre only one had thyroid antibodies (AT) in the blood. Among 182 adults with grade 1-2 goitre, examined within an area of low endemia, the frequency of AT was 7%, not significantly different from that found in the 286 persons with thyroid 'O' living in the same area. Among 181 adults with grade 2-3 goitre, examined within an area of serious endemia, the frequency of AT was 16%; the percentage went up to 24% in 144 patients operated on for goitre. AT frequency was 36% in 87 patients with toxic goitre, more than 70% in 97 patients with Graves' disease and 17% in 60 patients with cancer of the thyroid. AT occurred three times more frequently in women than in men. Microsomal antibodies were more frequently detected than anti-thyroglobulin antibodies: the opposite was true in thyroid cancer. Lymphocytic infiltration (IL) of the gland was observed in 45% of the 464 simple goitres and in 52% of the 60 cancers of the thyroid: it was more frequent and intense in women. Among the 144 patients operated on for goitre the frequency and the titre of AT progressed in parallel with the intensity of the lymphocytic infiltration. Patients with a greater lymphocytic infiltration and higher AT had a higher TSH. Multinodular non-toxic goitre and autoimmune lymphocytic thyroiditis can be present in the same thyroid gland and the clinical expression will depend on which condition predominates.